Masimirembwa Collen, Dandara Collet, Leutscher Peter Derek Christian
1 Department of Drug Metabolism and Pharmacokinetics & Medical Analytics, African Institute of Biomedical Science and Technology , Harare, Zimbabwe .
2 Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Cape Town, South Africa .
OMICS. 2016 Oct;20(10):575-580. doi: 10.1089/omi.2016.0120. Epub 2016 Sep 14.
The introduction of antiretroviral therapy (ART) led to huge reductions in human immunodeficiency virus (HIV)-related deaths, turning HIV-infection into a chronic condition. Attention is now turning to quality of life for patients on lifelong ART treatment, reflecting on the safety of antiretroviral drugs. In sub-Saharan Africa, efavirenz (EFV) forms the preferred first-line ART but adverse drug events have also been reported. We express our concern on EFV-based regimens being part of mass rollout programs without full attention to toxicities. EFV is associated with various neuropsychiatric adverse events (AEs). If EFV use is not monitored, a huge burden of neuropsychiatric AEs and elevated risk of drug resistance due to nonadherence are likely to follow. A monumental EFV-based ART regimen rollout program, through the UNAIDS 90-90-90 and option B plus programs/approaches, is planned, which will more than double the number of patients on EFV-containing ART. According to this ambitious treatment target, by 2020, 90% of all people living with HIV will know their HIV status; 90% of all people with diagnosed HIV infection will receive sustained ART; and 90% of all people receiving ART will have viral suppression. On the other hand, HIV patients of African origin are predisposed to developing EFV-induced neuropsychiatric AEs due to specific CYP2B6 genetic variants causing impaired metabolism of EFV. It is our considered opinion that the potential quantitative and qualitative burden of EFV-induced neuropsychiatric AEs, which can vary from person-to-person and between populations, deserve special attention and action during the ART rollout program. We here make a case for Africa in particular where we project the burden of neuropsychiatric AEs to be greatest. We advocate for surveillance of neuropsychiatric AEs due to EFV therapy, incorporation of pharmacogenetics testing for CYP2B6 to assist in EFV dosing, and measurement of plasma EFV concentration, as a three-pronged rational therapeutic drug monitoring strategy to guide EFV treatment toward precision medicine.
抗逆转录病毒疗法（ART）的引入使人类免疫缺陷病毒（HIV）相关死亡人数大幅减少，将HIV感染转变为一种慢性病。现在人们的注意力转向了接受终身ART治疗患者的生活质量，并开始思考抗逆转录病毒药物的安全性。在撒哈拉以南非洲地区，依非韦伦（EFV）是首选的一线ART药物，但也有药物不良事件的报道。我们对基于EFV的治疗方案在大规模推广项目中未充分关注毒性表示担忧。EFV与各种神经精神不良事件（AE）相关。如果不监测EFV的使用情况，可能会导致神经精神AE的巨大负担以及因不依从导致的耐药风险升高。一项基于EFV的ART治疗方案大规模推广项目正在通过联合国艾滋病规划署的90-90-90和选项B加计划/方法进行规划，这将使接受含EFV的ART治疗的患者数量增加一倍多。根据这一宏伟的治疗目标，到2020年，90%的HIV感染者将知晓自己的HIV感染状况；90%确诊感染HIV的人将接受持续的ART治疗；90%接受ART治疗的人将实现病毒抑制。另一方面，非洲裔HIV患者由于特定的CYP2B6基因变异导致EFV代谢受损，更容易发生EFV诱导的神经精神AE。我们经过深思认为，EFV诱导的神经精神AE的潜在定量和定性负担因人而异且因人群而异，在ART推广项目期间值得特别关注并采取行动。我们在此特别为非洲地区发声，预计该地区神经精神AE的负担最大。我们主张对EFV治疗引起的神经精神AE进行监测，纳入CYP2B6的药物遗传学检测以辅助EFV给药，并测量血浆EFV浓度，作为一种三管齐下的合理治疗药物监测策略，以指导EFV治疗走向精准医学。
